{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:36:14Z","timestamp":1770824174491,"version":"3.50.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2002,2,1]],"date-time":"2002-02-01T00:00:00Z","timestamp":1012521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T00:00:00Z","timestamp":1072742400000},"content-version":"vor","delay-in-days":697,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"BMBF project \u201cStructure, function and clinical significance of hepatitis B virus variants.\u201d"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Several naturally occurring variants of immunogenic T cell epitopes were identified within the hepatitis B surface antigen (HBsAg). The effect of these variants on the cellular immune response was studied in individuals vaccinated against HBV. Class-II restricted T-cell responses of 30 vaccinees were analyzed after stimulation of peripheral blood mononuclear cells (PBMCs) with 4 synthetic peptides representing the 4 T-cell epitopes of HBsAg known as of yet. The 2 epitopes P1 (aa 16-33) and P4 (aa 213-226) could be identified as the dominant ones in our vaccinees by proliferation assays and enzyme-linked immunospot assays. Responses to these epitopes were compared with responses to their naturally occurring variants found in HBV isolates of chronic virus carriers. Three of 11 variants of epitope P4 led to a complete loss of T-cell reactivity in 4 of 10 donors, all of whom reacted well to the corresponding wild-type sequence. The remaining 6 donors recognized these variants as well as the vaccine epitope. Similarly, 3 P1-variants of the 12 found induced only a significantly reduced reactivity in 4 of 10 donors, whereas they led to a normal response in the other 6 individuals. Stimulation of T cells also induced the secretion of antibody to HBsAg (anti-HBs) by specific B cells; however, those peptides that failed to activate T cells were also unable to cause any significant anti-HBs production. In conclusion, our results suggest an immune escape of certain mutant strains of HBV in vaccinated individuals could exist at the T-cell level.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2002.30903","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T03:46:10Z","timestamp":1030247170000},"page":"455-465","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":31,"title":["Variants of two major T cell epitopes within the hepatitis B surface antigen are not recognized by specific T helper cells of vaccinated individuals"],"prefix":"10.1097","volume":"35","author":[{"given":"Tanja","family":"Bauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Weinberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Jilg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2002.30903-BIB1|cit1","first-page":"745","volume-title":"Microbiology and Microbial Infections","volume":"1","author":"Kann","year":"1998"},{"key":"10.1053\/jhep.2002.30903-BIB2|cit2","first-page":"158","volume-title":"Vaccines","author":"Mahoney","year":"1999"},{"key":"10.1053\/jhep.2002.30903-BIB3|cit3","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/S0264-410X(98)00415-0","article-title":"Strategies to prevent and control hepatitis B and C virus infections: a global perspective","volume":"17","author":"Mast","year":"1999","journal-title":"Vaccine"},{"key":"10.1053\/jhep.2002.30903-BIB4|cit4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0140-6736(90)91874-A","article-title":"Vaccine-induced escape mutant of hepatitis B virus","volume":"336","author":"Carman","year":"1990","journal-title":"Lancet"},{"key":"10.1053\/jhep.2002.30903-BIB5|cit5","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0168-8278(97)80139-0","article-title":"Detection of different viral strains of hepatitis B virus in chronically infected children after seroconversion from HBsAg to anti-HBs indicating viral persistence","volume":"27","author":"Bahn","year":"1997","journal-title":"J Hepatol"},{"issue":"suppl 1","key":"10.1053\/jhep.2002.30903-BIB6|cit6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1365-2893.1997.tb00155.x","article-title":"The clinical significance of surface antigen variants of hepatitis B virus","volume":"4","author":"Carman","year":"1997","journal-title":"J Viral Hepat"},{"key":"10.1053\/jhep.2002.30903-BIB7|cit7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/hep.510270133","article-title":"Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis","volume":"27","author":"Ghany","year":"1998","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.30903-BIB8|cit8","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/hep.510270138","article-title":"Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation","volume":"27","author":"Protzer-Knolle","year":"1998","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.30903-BIB9|cit9","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1172\/JCI116148","article-title":"Loss of the common \u201cA\u201d determinant of hepatitis B surface antigen by a vaccine-induced escape mutant","volume":"90","author":"Waters","year":"1992","journal-title":"J Clin Invest"},{"key":"10.1053\/jhep.2002.30903-BIB10|cit10","first-page":"21","article-title":"Use of synthetic oligopeptides in identification and characterization of immunological functions in the amino acid sequence of the envelope protein of HIV-1","volume":"2","author":"Modrow","year":"1989","journal-title":"J Acquir Immune Defic Syndr"},{"key":"10.1053\/jhep.2002.30903-BIB11|cit11","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1053\/gast.1997.v112.pm9178695","article-title":"Epitope specificity of Th0\/Th2 CD4+ T-lymphocyte clones induced by vaccination with rHBsAg vaccine","volume":"112","author":"Honorati","year":"1997","journal-title":"Gastroenterology"},{"key":"10.1053\/jhep.2002.30903-BIB12|cit12","first-page":"283","article-title":"In vitro anti-HBs antibody synthesis from anti-hepatitis B vaccine recipients","volume":"70","author":"Barnaba","year":"1987","journal-title":"Clin Exp Immunol"},{"key":"10.1053\/jhep.2002.30903-BIB13|cit13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1046\/j.1365-2249.1996.d01-732.x","article-title":"Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection","volume":"105","author":"B\u00f6cher","year":"1996","journal-title":"Clin Exp Immunol"},{"key":"10.1053\/jhep.2002.30903-BIB14|cit14","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/BF00163994","article-title":"Normal HBsAg presentation and T-cell defect in the immune response of nonresponders","volume":"41","author":"Salazar","year":"1995","journal-title":"Immunogenetics"},{"key":"10.1053\/jhep.2002.30903-BIB15|cit15","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.4049\/jimmunol.140.6.1808","article-title":"Recognition of hepatitis B surface antigen by human T lymphocytes. Proliferative and cytotoxic responses to a major antigenic determinant defined by synthetic peptides","volume":"140","author":"Celis","year":"1988","journal-title":"J Immunol"},{"key":"10.1053\/jhep.2002.30903-BIB16|cit16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000150412","article-title":"Hepatitis B surface antigen variation and protective immunity","volume":"38","author":"Howard","year":"1995","journal-title":"Intervirology"},{"key":"10.1053\/jhep.2002.30903-BIB17|cit17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000150411","article-title":"Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene","volume":"38","author":"Magnius","year":"1995","journal-title":"Intervirology"},{"key":"10.1053\/jhep.2002.30903-BIB18|cit18","first-page":"138","volume-title":"Viral Hepatitis and Liver Disease","author":"Weinberger","year":"1997"},{"key":"10.1053\/jhep.2002.30903-BIB19|cit19","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1099\/0022-1317-81-5-1165","article-title":"High genetic variability of the group-specific a-determinant of hepatitis B surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic carriers lacking detectable HBsAg in serum","volume":"1","author":"Weinberger","year":"2000","journal-title":"J Gen Virol"},{"key":"10.1053\/jhep.2002.30903-BIB20|cit20","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/336778a0","article-title":"A malaria T-cell epitope recognized in association with most mouse and human MHC class II molecules","volume":"336","author":"Sinigaglia","year":"1988","journal-title":"Nature"},{"key":"10.1053\/jhep.2002.30903-BIB21|cit21","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/hep.510290120","article-title":"Kinetics of hepatitis B surface antigen-specific immune responses in acute and chronic hepatitis B or after HBs vaccination: stimulation of the in vitro antibody response by interferon gamma","volume":"29","author":"B\u00f6cher","year":"1999","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.30903-BIB22|cit22","first-page":"197","article-title":"HBsAg-induced interferon-gamma secretion in T cells from asymptomatic HBsAg carriers and HB-immune donors in vitro","volume":"70","author":"Sylvan","year":"1990","journal-title":"Immunology"},{"key":"10.1053\/jhep.2002.30903-BIB23|cit23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1365-3083.1991.tb01566.x","article-title":"There is no correlation between function and lymphokine production of HBs-antigen-specific human CD4(+)-cloned T cells","volume":"34","author":"Tsutsui","year":"1991","journal-title":"Scand J Immunol"},{"key":"10.1053\/jhep.2002.30903-BIB24|cit24","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4049\/jimmunol.137.1.315","article-title":"Immune response to the pre-S(1) region of the hepatitis B surface antigen (HBsAg): a pre-S(1)-specific T cell response can bypass nonresponsiveness to the pre-S(2) and S regions of HBsAg","volume":"137","author":"Milich","year":"1986","journal-title":"J Immunol"},{"key":"10.1053\/jhep.2002.30903-BIB25|cit25","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0168-8278(88)80032-1","article-title":"Persistence of specific antibodies after hepatitis B vaccination","volume":"6","author":"Jilg","year":"1988","journal-title":"J Hepatol"},{"key":"10.1053\/jhep.2002.30903-BIB26|cit26","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/hep.510270243","article-title":"Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective","volume":"27","author":"Melegari","year":"1994","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.30903-BIB27|cit27","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/hep.510290119","article-title":"Transient selection of a hepatitis B virus polymerase gene mutant associated with a decreased replication capacity and famciclovir resistance","volume":"29","author":"Pichoud","year":"1999","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.30903-BIB28|cit28","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0168-8278(98)80191-8","article-title":"Drug therapy for chronic hepatitis B antiviral efficacy and influence of hepatitis B virus polymerase mutations on the outcome of therapy","volume":"29","author":"Zoulim","year":"1998","journal-title":"J Hepatol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2002.30903","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2002.30903","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200202000-00029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T15:54:02Z","timestamp":1738943642000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200202000-00029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,2]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2002.30903","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2002,2]]}}}